Evaluation of the Antiviral Pharmacodynamic Effect, Safety, and Pharmacokinetics of Escalating Doses of BILB 1941 ZW to Patients With Chronic Hepatitis C Genotype 1 Virus Infection
Primary Purpose
Hepatitis C, Chronic
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
BILB 1941 ZW
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C, Chronic
Eligibility Criteria
Inclusion Criteria:
- Adult males from 18 - 65 years
- Written informed consent consistent with ICH (International Conference on Harmonisation)/GCP (Good Clinical Practice) and local legislation given prior to any study procedures
- Chronic HCV infection demonstrated by positive HCV IgG Antibody
- HCV genotype 1 which has to be confirmed by central laboratory test before Visit 2
- Liver biopsy consistent with active Hepatitis C virus (HCV) infection obtained within the last 24 months showing minimal to mild liver fibrosis and without cirrhosis (Ishak or Metavir grade <= 2)
- HCV ribonucleic acid (RNA) load greater than 100,000 IU RNA per ml serum at screening
- Willing to abstain from alcohol during the screening, treatment and until completion of the study (visit 11)
Exclusion Criteria:
- Males not using an adequate form of contraception (condom, sterilisation at least 6 months post operation) in case their partner is of childbearing potential and is not using an adequate form of contraception (hormonal contraceptives, oral or injectable/implantable, intra-uterine device (IUD).
- Any other or additional plausible cause for chronic liver disease, including the presence of other viruses known or suspected to cause hepatitis
- Evidence of decompensated liver disease: ascites, portal hypertension or hepatic encephalopathy
- Positive test for human immunodeficiency virus (HIV) or Hepatitis B surface (HBs) antigen at screening
- Current alcohol or drug abuse, or history of the same, within the past twelve (12) months. All patients must abstain from alcohol from enrolment until completion of the study (visit 11).
- Any concurrent medical illness or disease requiring treatment or concomitant medications
- History of malignancy (except for previously cured squamous cell or basal cell carcinoma)
- Usage of any investigational drug within thirty (30) days prior to enrolment or 5 halflives, whichever is longer; or the planned usage of an investigational drug during the course of the current study
- Patients treated with interferon and/or ribavirin within 6 months prior to screening
- Planned or concurrent usage of any other pharmacological therapy at screening, or during the trial period, including any antiviral therapy or vaccination
- Known hypersensitivity to drugs or excipients
Patients with any one of the following laboratory values at screening:
- Alanine transaminase (ALT) or Aspartate transaminase (AST) > 2.5 x upper limit of normal (ULN) (at screening and during the last 3 months before screening demonstrated by at least 2 further determinations)
- Total bilirubin > 1x ULN
- Alkaline phosphatase > 1.5x ULN
- Prothrombin time (INR, prolonged) > 1.5
- Platelet count < 100,000 / mm3
- Hemoglobin < 10.5 g/dL
- White blood cell count < 2,000 / mm3
- Patients with any clinically significant laboratory abnormalities based on the investigator's medical assessment at screening
- Positive urine test for drug abuse at screening
- Patients with known Gilbert's disease
- Prior randomisation to active treatment with BILB 1941 ZW into dose groups 3 - 9 of this trial, or previous re-treatment based on amendment 2. To support selection, centers will receive lists of the placebo patients of the previous dose levels, however, only for each center separately
- Inability to comply with the protocol
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
BILB 1941 ZW
Placebo
Arm Description
Escalating Doses
Outcomes
Primary Outcome Measures
Change in virus load (VL)
determined by IU per ml serum from baseline by > 1.0 log10 step
Secondary Outcome Measures
Cmax (maximum measured concentration of the analyte in plasma)
tmax (time from dosing to maximum measured concentration of the analyte in plasma)
AUCτ,1 (area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ after administration of the first dose)
AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
%AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation)
λz (terminal rate constant in plasma)
t1/2 (terminal half-life of the analyte in plasma)
CL/F (apparent clearance of the analyte in plasma after extravascular administration)
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular administration)
Number of patients with clinically significant changes in vital signs
Number of patients with clinically significant changes in body temperature
Number of patients with abnormal findings in electrocardiogram (ECG)
Number of patients with abnormal changes in clinical laboratory parameters
Number of patients with adverse events
Number of patients with abnormal findings in physical examination
Investigator assessed tolerability on a 4 point scale
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02254707
Brief Title
Evaluation of the Antiviral Pharmacodynamic Effect, Safety, and Pharmacokinetics of Escalating Doses of BILB 1941 ZW to Patients With Chronic Hepatitis C Genotype 1 Virus Infection
Official Title
A Multinational Randomised, Double-blind, Placebo Controlled Study to Evaluate the Antiviral Pharmacodynamic Effect, Safety, and Pharmacokinetics of Escalating Doses of BILB 1941 ZW Oral Solution Administered Q8H for Five Days to Patients With Chronic Hepatitis C Genotype 1 Virus Infection
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
July 2004 (undefined)
Primary Completion Date
April 2006 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
To assess the antiviral effect, safety and pharmacokinetics of rising doses of 10 mg, 20 mg, 40 mg, 60 mg, 80 mg, 100 mg, 150 mg, 200 mg, 300 mg, 450 mg, 650 mg, 900 mg oral BILB 1941 ZW administered Q8H in a polyethyleneglycol 400 (PEG 400): distilled water: Tromethamine (TRIS) drinking solution for five days to patients with chronic HCV genotype 1 infection
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
96 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BILB 1941 ZW
Arm Type
Experimental
Arm Description
Escalating Doses
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
BILB 1941 ZW
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Change in virus load (VL)
Description
determined by IU per ml serum from baseline by > 1.0 log10 step
Time Frame
Up to day 6
Secondary Outcome Measure Information:
Title
Cmax (maximum measured concentration of the analyte in plasma)
Time Frame
Up to 14 days after first drug administration
Title
tmax (time from dosing to maximum measured concentration of the analyte in plasma)
Time Frame
Up to 14 days after first drug administration
Title
AUCτ,1 (area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ after administration of the first dose)
Time Frame
Up to 14 days after first drug administration
Title
AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Time Frame
Up to 14 days after first drug administration
Title
%AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation)
Time Frame
Up to 14 days after first drug administration
Title
λz (terminal rate constant in plasma)
Time Frame
Up to 14 days after first drug administration
Title
t1/2 (terminal half-life of the analyte in plasma)
Time Frame
Up to 14 days after first drug administration
Title
CL/F (apparent clearance of the analyte in plasma after extravascular administration)
Time Frame
Up to 14 days after first drug administration
Title
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular administration)
Time Frame
Up to 14 days after first drug administration
Title
Number of patients with clinically significant changes in vital signs
Time Frame
Up to 14 days after first drug administration
Title
Number of patients with clinically significant changes in body temperature
Time Frame
Up to 14 days after first drug administration
Title
Number of patients with abnormal findings in electrocardiogram (ECG)
Time Frame
Up to 14 days after first drug administration
Title
Number of patients with abnormal changes in clinical laboratory parameters
Time Frame
Up to 14 days after first drug administration
Title
Number of patients with adverse events
Time Frame
Up to 14 days after first drug administration
Title
Number of patients with abnormal findings in physical examination
Time Frame
Up to 14 days after first drug administration
Title
Investigator assessed tolerability on a 4 point scale
Time Frame
Up to 14 days after first drug administration
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult males from 18 - 65 years
Written informed consent consistent with ICH (International Conference on Harmonisation)/GCP (Good Clinical Practice) and local legislation given prior to any study procedures
Chronic HCV infection demonstrated by positive HCV IgG Antibody
HCV genotype 1 which has to be confirmed by central laboratory test before Visit 2
Liver biopsy consistent with active Hepatitis C virus (HCV) infection obtained within the last 24 months showing minimal to mild liver fibrosis and without cirrhosis (Ishak or Metavir grade <= 2)
HCV ribonucleic acid (RNA) load greater than 100,000 IU RNA per ml serum at screening
Willing to abstain from alcohol during the screening, treatment and until completion of the study (visit 11)
Exclusion Criteria:
Males not using an adequate form of contraception (condom, sterilisation at least 6 months post operation) in case their partner is of childbearing potential and is not using an adequate form of contraception (hormonal contraceptives, oral or injectable/implantable, intra-uterine device (IUD).
Any other or additional plausible cause for chronic liver disease, including the presence of other viruses known or suspected to cause hepatitis
Evidence of decompensated liver disease: ascites, portal hypertension or hepatic encephalopathy
Positive test for human immunodeficiency virus (HIV) or Hepatitis B surface (HBs) antigen at screening
Current alcohol or drug abuse, or history of the same, within the past twelve (12) months. All patients must abstain from alcohol from enrolment until completion of the study (visit 11).
Any concurrent medical illness or disease requiring treatment or concomitant medications
History of malignancy (except for previously cured squamous cell or basal cell carcinoma)
Usage of any investigational drug within thirty (30) days prior to enrolment or 5 halflives, whichever is longer; or the planned usage of an investigational drug during the course of the current study
Patients treated with interferon and/or ribavirin within 6 months prior to screening
Planned or concurrent usage of any other pharmacological therapy at screening, or during the trial period, including any antiviral therapy or vaccination
Known hypersensitivity to drugs or excipients
Patients with any one of the following laboratory values at screening:
Alanine transaminase (ALT) or Aspartate transaminase (AST) > 2.5 x upper limit of normal (ULN) (at screening and during the last 3 months before screening demonstrated by at least 2 further determinations)
Total bilirubin > 1x ULN
Alkaline phosphatase > 1.5x ULN
Prothrombin time (INR, prolonged) > 1.5
Platelet count < 100,000 / mm3
Hemoglobin < 10.5 g/dL
White blood cell count < 2,000 / mm3
Patients with any clinically significant laboratory abnormalities based on the investigator's medical assessment at screening
Positive urine test for drug abuse at screening
Patients with known Gilbert's disease
Prior randomisation to active treatment with BILB 1941 ZW into dose groups 3 - 9 of this trial, or previous re-treatment based on amendment 2. To support selection, centers will receive lists of the placebo patients of the previous dose levels, however, only for each center separately
Inability to comply with the protocol
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com
Description
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Evaluation of the Antiviral Pharmacodynamic Effect, Safety, and Pharmacokinetics of Escalating Doses of BILB 1941 ZW to Patients With Chronic Hepatitis C Genotype 1 Virus Infection
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